Small-scale Biomanufacturing Benefits from Disposable Bioreactors - Two-compartment bioreactors combine high cell density yields with an easy-to-use design for optimum biomanufacturing results - BioPh


Small-scale Biomanufacturing Benefits from Disposable Bioreactors
Two-compartment bioreactors combine high cell density yields with an easy-to-use design for optimum biomanufacturing results

BioPharm International
Volume 18, Issue 12

Further cost savings are possible during downstream processing of the product. Owing to the high concentration of the produced MAb, concentrating it prior to purification is not necessary. Depending on the application of the MAb, purification might be omitted as well, because the MAb purity, i.e., the ratio of MAb to contaminants, is much higher than the purity of MAbs produced with conventional systems.

According to the analysis presented here, total production costs are lowest when CELLine is used (€1.5/mg MAb, or approximately $1.85/mg MAb), and they increase by 60 percent when using roller bottles (€2.4/mg MAb, or approximately $2.96/mg MAb), primarily resulting from higher expenses for serum and labor. The production with a stirred bioreactor further augments the costs, due to additional labor and to equipment amortization. It should be noted, however, that costs depend on the amount of MAb produced: for small amounts (less than 50 mg) the difference between roller bottles and CELLine is small and economic considerations are less relevant. For larger amounts (greater than 1 g), the use of a stirred bioreactor becomes competitive and represents an alternative to CELLine.


The CELLine bioreactor combines the advantages of high cell densities achieved in two-compartment systems with the ease of use typical of a standard tissue culture flask, resulting in economically efficient biomanufacturing on a small to medium scale. The presented benefits of MAb production with CELLine also apply to the manufacturing of other biological products such as recombinant proteins and viral vectors, so that any laboratory with basic cell culture expertise can produce highly concentrated, high-quality proteins for research or diagnostic purposes in a cost-efficient way.5-7

Fabrizio Baumann is product manager for cell cultivation at INTEGRA Biosciences AG, Schonbühlstr. 8, CH - 7000 Chur, Switzerland, phone: +41 (0), Fax: +41(0),


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2. Trebak M, Chong JM, Herlyn D, Speicher DW. Efficient laboratory-scale production of monoclonal antibodies using membrane-based high-density cell culture technology. J Immunol Methods. 1999; 230(1-2):59-70.

3. Bruce MP, Boyd V, Duch C, White JR. Dialysis-based bioreactor systems for the production of monoclonal antibodies — alternatives to ascites production in mice. J Immunol Methods. 2002; 264(1-2):59-68.

4. McArdle J. Report of the workshop on monoclonal antibodies). ATLA. 2004; 32 (suppl 1):119-122.

5. Mittermaier J, Zang-Gandor MO. Long-term high level protein expression in adherent, protein-free growing BHK cells using INTEGRA CELLine adhere 1000 bio-reactor flasks. Genetic Engineering News. 2004; 24(12):42.

6. Docagne F, Colloc'h N, Bougueret V, et al. A soluble transforming growth factor-beta (TGF-beta) type I receptor mimics TGF-beta responses. J Biol Chem. 2001; 276(49):46243-46250.

7. Matsumoto I, Studer A. Continuous recombinant protein production in baculovirus infected SF9 cells using CELLine classic 1000 two-compartment bioreactors. 2004. Available at:

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